Lactoferrin stimulates the production of leucocyte migration inhibitory factor by human peripheral mononuclear leucocytes.

The effect of lactoferrin on the migration of human polymorphonuclear cells was investigated. High concentrations of lactoferrin (greater than 250 micrograms/ml) markedly inhibited the migration of granulocytes under agarose. This migration inhibition could not be neutralized by an antibody against leucocyte migration inhibitory factor (LIF), suggesting a direct effect of lactoferrin on the granulocytes. Low concentrations of lactoferrin were, however, indirectly capable of inhibiting neutrophil migration. The overnight culture of mononuclear leucocytes with low concentrations of lactoferrin (10 micrograms/ml) resulted in the release of granulocyte migration inhibiting factors in the cell free culture supernatant. Strong evidence indicating that the migration inhibiting factors were due to LIF, was obtained in experiments whereby the inhibitory activity could be completely neutralized by anti-LIF antibodies. The lactoferrin-mediated stimulation of LIF release by mononuclear leucocytes could be neutralized by an anti-lactoferrin serum, but not by an anti-albumin serum, whereas PPD-induced LIF release was not affected by either antiserum. These findings suggest that lactoferrin besides its well known anti-microbial properties, may also play a regulatory role in the migratory response of polymorphonuclear cells during inflammatory conditions.